title: Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy.
abstract: OBJECTIVE
  Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)-naïve patients with breast cancer-related bone metastases.
  
  
  METHODS
  Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks).
  
  
  RESULTS
  At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were -73% and -75% for the pooled denosumab groups and -79% and -71% for the IV BP group. Among patients with > or =1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP-treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP-treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred.
  
  
  CONCLUSIONS
  In IV BP-naïve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA. alipton@psu.edu
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Jazmin
authors.initials: J
authors.lastname: Figueroa
authors.forename: Cristina
authors.initials: C
authors.lastname: Alvarado
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Celigny
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Body
authors.forename: Richard
authors.initials: R
authors.lastname: de Boer
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Pere
authors.initials: P
authors.lastname: Gascon
authors.forename: Katia S
authors.initials: KS
authors.lastname: Tonkin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Alexander H G
authors.initials: AH
authors.lastname: Paterson
authors.forename: Guozhi M
authors.initials: GM
authors.lastname: Gao
authors.forename: Amy C
authors.initials: AC
authors.lastname: Kinsey
authors.forename: Mark C
authors.initials: MC
authors.lastname: Peterson
authors.forename: Susie
authors.initials: S
authors.lastname: Jun
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007390:International Agencies; D008875:Middle Aged; D011379:Prognosis; D053245:RANK Ligand / Q000627:therapeutic use*; D012449:Safety; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053245:RANK Ligand; D000069448:Denosumab